Evidence map›Paper›PMID 32799103›Full record

ArticleAtherosclerosis2020

Nullifying epigenetic writer DOT1L attenuates neointimal hyperplasia.

Yitao Huang, Go Urabe, Mengxue Zhang, Jing Li, Hatice Gulcin Ozer, Bowen Wang, K Craig Kent, Lian-Wang Guo

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Atherosclerosis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 19 citations in OpenAlex.

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  6. The evaluation of six genes combined value in glioma diagnosis and prognosis.Journal of cancer research and clinical oncology · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Yitao HuangDepartment of Surgery, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA; Department of Physiology & Cell Biology, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA.
Go UrabeDepartment of Surgery, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA; Department of Physiology & Cell Biology, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA.
Mengxue ZhangDepartment of Surgery, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA; Department of Physiology & Cell Biology, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA.
Jing LiDepartment of Surgery, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA; Department of Physiology & Cell Biology, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA.
Hatice Gulcin OzerDepartment of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Bowen WangDepartment of Surgery, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA; Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA.
K Craig KentDepartment of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Lian-Wang GuoDepartment of Surgery, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA; Department of Physiology & Cell Biology, College of Medicine and Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, 43210, USA; Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA. Electronic address: lg8zr@virginia.edu.
The Ohio State University Wexner Medical Center · USUniversity of Virginia · USThe Ohio State University · US

Funding

Targeting PERK: An Endothelium-Protective Stent-Free Strategy for Mitigation of Intimal Hyperplasia After Vascular SurgeryR01HL143469 · NHLBI · UNIVERSITY OF VIRGINIA · PI GONG, SHAOQIN -, GUO, LIANWANG · 2018 to 2021
$2.4M
Development of unimolecular nanoparticle-mediated periadventitial drug delivery system for sustained and targeted inhibition of intimal hyperplasia following open vascular reconstructionR01HL129785 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GUO, LIANWANG, KENT, K CRAIG · 2016 to 2019
$2.0M
BET Bromodomain proteins as Novel Epigenetic Targets for prevention of Intimal Hyperplasia after Vascular SurgeryR01HL133665 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GUO, LIANWANG · 2016 to 2019
$1.6M
Master epigenetic regulators and retinal degenerative diseaseR01EY029809 · NEI · UNIVERSITY OF VIRGINIA · PI GUO, LIANWANG · 2019 to 2022
$1.6M
NEI NIH HHS R01 EY029809NHLBI NIH HHS R01 HL129785NHLBI NIH HHS R01 HL133665NHLBI NIH HHS R01 HL143469
6 · The paper itself

Abstract

BACKGROUND AND

aimsHistone methyltransferases are emerging targets for epigenetic therapy. DOT1L (disruptor of telomeric silencing 1-like) is the only known methylation writer at histone 3 lysine 79 (H3K79). It is little explored for intervention of cardiovascular disease. We investigated the role of DOT1L in neointimal hyperplasia (IH), a basic etiology of occlusive vascular diseases. METHODS AND

resultsIH was induced via balloon angioplasty in rat carotid arteries. DOT1L and its catalytic products H3K79me2 and H3K79me3 (immunostaining) increased by 4.69 ± 0.34, 2.38 ± 0.052, and 3.07 ± 0.27 fold, respectively, in injured (versus uninjured) carotid arteries at post-injury day 7. Dot1l silencing via shRNA-lentivirus infusion in injured arteries reduced DOT1L, H3K79me2, and IH at day 14 by 54.5%, 37.1%, and 76.5%, respectively. Moreover, perivascular administration of a DOT1L-selective inhibitor (EPZ5676) reduced H3K79me2, H3K79me3, and IH by 56.1%, 58.6%, and 39.9%, respectively. In addition, Dot1l silencing and its inhibition (with EPZ5676) in vivo in injured arteries boosted smooth muscle α-actin immunostaining; pretreatment of smooth muscle cells with EPZ5676 in vitro reduced pro-proliferative marker proteins, including proliferating cell nuclear antigen (PCNA) and cyclin-D1.

conclusionsWhile DOT1L is upregulated in angioplasty-injured rat carotid arteries, either its genetic silencing or pharmacological inhibition diminishes injury-induced IH. As such, this study presents a strong rationale for continued mechanistic and translational investigation into DOT1L targeting for treatment of (re)stenotic vascular conditions.

Indexed as

Histone-Lysine N-MethyltransferaseNeointimaAnimalsGene SilencingHistonesHyperplasiaRatsHistone-Lysine N-MethyltransferaseHistonesDOT1LEpigenetic targetH3K79 methylationIn vivo silencingNeointimal hyperplasia

Identifiers

PMID32799103
PMCPMC7503165
OpenAlexW3038382595

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.